Diabetes: The Problem

The team at KDAH have recently been approved for Pancreas and Small Bowel Transplant and are listing patients for both.

Type 1 diabetes mellitus afflicts the lives of millions of Indians. Type 1 diabetes usually is diagnosed in children and young adults, leading to the term "juvenile diabetes." The more common form of diabetes is type 2 diabetes, also known as "adult-onset diabetes." In both forms of diabetes, the body is unable to keep the blood sugar levels under proper control. High blood sugar levels can damage many parts of the body. Patients with diabetes often suffer from kidney failure, blindness, nerve problems, hardening of the arteries and other problems because the blood sugar is too high.

The pancreas gland makes insulin, but also has many other functions. Most of the pancreas gland makes juices that help digest food. Doctors now know that special cells found within the islets, called beta cells, make the hormone insulin that keeps the blood sugar under proper control. In type 1 diabetes, doctors think the patient's own immune system destroys the beta cells. All patients with type 1 diabetes need insulin shots to keep the blood sugar under control, leading to the common name "insulin dependent diabetes."

Transplantation is well suited to the treatment of type 1 diabetes. The transplant provides the recipient with replacement beta cells. Transplantation of the whole pancreas gland now provides many type 1 patients with freedom from insulin treatment. Transplantation of only the islets after separating them from the rest of the pancreas is under study.

Type 2 diabetes is different. Type 2 diabetes has many causes. Diet, weight loss and exercise can often help type 2 patients get their blood sugars under control. If the blood sugars are still too high, medications can often help. If none of these treatments helps keep the blood sugar under control, then patients with type 2 diabetes may need insulin shots. Even though some patients with type 2 diabetes may eventually need insulin shots, many refer to type 2 diabetes as "non-insulin dependent diabetes." Although doctors are now finding type 2 diabetes in teenagers, the onset of this disease usually occurs in adults, leading to the other common name of "adult-onset diabetes." Doctors know that insulin resistance characterizes type 2 diabetes, meaning that the body does not use the insulin produced by the beta cells normally. Eventually the beta cells in type 2 patients may wear out from overworking.

In summary, a lack of insulin producing beta cells causes type 1 diabetes (also known as juvenile-onset or insulin-dependent diabetes mellitus), and replacement of the beta cells through transplantation is the only current treatment that provides freedom from insulin therapy. Insulin resistance characterizes type 2 diabetes (also known as adult onset or non-insulin-dependent diabetes mellitus), and transplantation is an accepted treatment option for these patients

Indications & Contraindications

The clinical practice recommendations of the American Diabetes Association state that a pancreas transplant (Simultaneous Kidney and Pancreas Transplant [SPK] or Pancreas After Kidney Transplant [PAK] is an acceptable surgical procedure in type 1 diabetic patients also undergoing kidney transplantation. These must be in medically suitable type 1 diabetic patient who are also renal transplant candidates or who have excellent function of a kidney transplant who is interested in receiving a pancreas transplant. The vast majority of pancreas transplants are performed as an SPK followed by PAK.

Pancreas transplantation alone [PTA] should be performed before secondary complications of diabetes become irreversible and before the need for a kidney transplant. A creatinine clearance above 60 to 70 mL/min is usually required as immunosuppressant can cause accelerated deterioration of native renal function in patients with a lower creatinine clearance.

Types of Procedures

There are three groups of patients that are considered for pancreas transplantation. First is the simultaneous kidney and pancreas transplantation (or SPK) for diabetics who are in renal failure. This is generally the preferred method of pancreas transplantation having the advantage of only one surgical intervention and one source of foreign antigen for the recipient patient.

Second is pancreas after kidney transplant (or PAK) for diabetic patients who already have a functioning kidney allograft. Immunosuppressive therapy is not a major concern as patients are already immunosuppressed for their kidney allograft. The main risk to the patient is the alteration in immunosuppression necessary after pancreas transplantation and the inherent risks of an intra abdominal surgical procedure. In general, type 1 diabetic patients undergoing living or cadaveric renal transplantation should have their kidney placed on the left side in anticipation of a pancreas transplant in the future.

Third is the pancreas transplantation alone (or PTA). This is a therapeutic option of the pre uremic patient with none to minimal renal dysfunction who has brittle diabetic management despite the administration of conventional anti diabetic therapies and hypoglycemic unawareness. The main risks to these patients are the long-term effects of chronic immunosuppression and the surgical procedure itself.

FAQs

This section is for patients with diabetes who are considering a combined kidney
Pancreas transplant or a pancreas only transplant.

What is the pancreas and why is it transplanted?

The pancreas is an organ inside the abdomen, which consists of 2 different types of
tissue with 2 separate functions. Most of the pancreas is a gland that secretes a fluid
rich in digestive enzymes. This helps digestion of the food we eat. About 2-3% of
the pancreas consists of 'endocrine' tissue, which is a cluster of cells (islets) that
secretes small amounts of hormones into the bloodstream. The most important one
amongst these hormones is insulin. The lack of insulin causes diabetes. Pancreas
transplants are performed to treat diabetes.

Can all diabetic patients be treated by pancreas transplantation?

No. Only patients suffering from the so-called 'type I' diabetes mellitus lack insulin
as a result of self-destruction of their insulin producing islets. Such patients can
be given a further source of islets by pancreas transplantation. 'Type II' diabetes
is much more common. In this disease the problem is not lack of insulin, but
a resistance to the action of insulin on other tissues. Some patients with type II
diabetes may require insulin injections later during the course of their disease.
Pancreas transplantation is only suitable for patients with type I diabetes and a selected
few with type 2 disease.

What does pancreas transplantation offer to a diabetic individual?

People with type I diabetes require lifelong treatment with regular injections
of insulin (usually a few times each day). Pancreas transplantation is the only
treatment for diabetes that can restore complete insulin independence and normal
blood sugar levels. Patients after successful pancreas transplantation do not need
insulin, have no special dietary requirements, do not need to pierce themselves
regularly to check their blood sugar levels and are not at any risk of becoming
hypoglycemic.

It is also known that most of the complications of diabetes are related to blood
sugar control such as:

Retinopathy leading to blindness

Nephropathy leading to kidney failure

Neuropathy which may cause foot ulcers

Digestive problems

Abnormalities of heart rhythm

Hypoglycemic unawareness

Angiopathy and accelerated atherosclerosis

Strict and good blood sugar control in diabetic patients is associated with a delay
in the onset and a reduction in the severity of complications and perhaps even
prevention of some complications. Since there is no better means of blood sugar
control than successful pancreas transplantation, this operation should benefit
Diabetic patients by preventing or helping some of the long-term complications
of diabetes.

How certain are we that pancreas transplantation can prevent complications Related to Diabetes?

There is a substantial amount of convincing indirect evidence about the potential
influence of successful pancreas transplantation on long-term diabetic complications.
We can say with a reasonable degree of confidence that successful pancreas
transplantation will prevent or even reverse early changes of diabetic nephropathy
such that diabetic patients will not continue to develop end stage kidney failure and
require dialysis. There is also reasonably good evidence showing that successful
pancreas transplantation can prevent or partially reverse diabetic neuropathy.

The amount of benefit that one can expect from the pancreas transplant depends
on when exactly the transplant is performed in the course of the disease. End stage
retinopathy with blindness or significant neuropathy and vascular disease, which
may have necessitated amputation, clearly represent very advanced and irreversible
complications, which cannot be improved by pancreas transplantation.

Do diabetic patients receiving pancreas transplants live longer?

Almost all studies have shown better long-term survival in diabetic patients
who have been treated with pancreas transplantation compared with those
who have been treated with insulin. It may be that younger and fitter
diabetic patients receive pancreas transplants whereas older diabetics with other
health problems are those who remain on insulin. Better long-term survival rates
with pancreas transplantation could therefore be simply a reflection of patient
selection. However more recent data in the scientific literature suggests that
pancreas transplantation does confer a genuine survival advantage to diabetic
patients. This is probably related to the influence of pancreas transplantation
on long-term diabetic complications. Five or 10 years after transplantation the
difference in the survival prospects for patients with transplants is considerably
different to those who remain on insulin.

Why don't we offer pancreas transplantation to all patients with
type 1 diabetes?

Mainly because it has risks. Lifelong treatment with insulin injections is still safer
for most patients with type I diabetes. Even if pancreas transplantation could be
made much safer, there would be the problem of shortage of organ donors to
provide the number of pancreas transplants that we need to perform to meet the
demand.

Transplantation of the pancreas involves a major operation. Like all surgical
procedures this puts the patient at risk of complications and even a small chance of
death. Recent advances in surgical techniques and other medications that are used
have greatly improved the safety of the pancreas transplant operation, such that
around 97-98% of patients undergoing pancreas transplants will survive.

Other complications such as bleeding and infection are not rare and about 1 in 4 patients
undergoing a pancreas transplant will require at least 1 more operation to deal
with complications. Other risks relate to the medication that patients need to
use after transplantation.

Pancreas transplants like other organ transplants involve transfer of foreign tissue,
which would undergo rejection in normal circumstances. It is therefore necessary to use medication to suppress the immune system in order to prevent the rejection of the
transplanted organs. These medicines (immunosuppressant) have many potentially
serious side effects such as increased risk of infection and even a small increase in the probability of developing cancer.

How successful are pancreas transplants?

The success rate expressed as the probability of being cured of diabetes (not
needing any insulin) 1 year after the transplant is about 85%. This is similar to
the success rate of other organ transplants such as kidney, liver or heart transplants.
In the longer-term (beyond 1 year) patients with pancreas transplants are likely to
do at least as well as those with other types of organ transplants.

Diabetes can also cause kidney failure. Can such patients need kidney transplants?

Yes. In fact if a diabetic patient requires a kidney transplant in order to treat
kidney failure, they can also be given a pancreas transplant at the same time. This
type of double transplant (simultaneous pancreas kidney transplant) is particularly
attractive since patients have already been selected for one transplant, which
requires immunosuppression. With only minimal additional risk it is possible to
treat diabetes as well as treating kidney failure.

What about diabetic patients who do not have kidney failure, can they receive pancreas transplants?

Yes they can, but this will be appropriate in only a very small proportion of diabetic
patients. As discussed above, for most diabetic patients without kidney failure
lifelong treatment with insulin, despite its problems and the inconvenience, is still
safer than a pancreas transplant. However a small number of diabetic patients
have life threatening complications of diabetes (for example hypoglycemic
unawareness). In such patients benefits of a pancreas transplant outweigh the risks,
indeed a pancreas transplant can be life saving.

Why is the whole pancreas transplanted, when it is only the Insulin producing islets that are needed?

Insulin producing cells make up only around 2% of the pancreas
gland. If these islets could be separated from the remainder of the pancreas
gland they could be transplanted with a very simple procedure similar to a
blood transfusion. This has been tried for many years without much success
for various technical reasons. We are making progress and only in the past year
or so a small number of patients have received successful islet transplants. This
is obviously attractive because the surgical risks of a major operation can be
avoided. However even then patients receiving islet transplants do require lifelong
immunosuppressive medication with potentially serious side effects.

Are islet transplants going to replace pancreas transplants in the future?

Difficult to know. Problems with islet transplantation are profound and it is not
yet a common successful procedure. We are making some progress but at least for
the foreseeable future, the only realistic option to make diabetic patients independent of
insulin will still be a pancreas transplant.

How long will I be in hospital for?

This depends on each individual patient and how they recover from their operation
and how well the organs function. It is usually around 14 – 21 days.

How long will I be away from work?

In the early weeks after a transplant, there is a need to review patients at the
out-patients clinic very frequently. Therefore even if all goes very well, return to
work is not practical before 2 months. Most patients will be off work for about
three months, some longer.

How do you know if the pancreas is functioning?

If the pancreas functions well you will not need any insulin after your operation
and your blood sugar will be normal.

Team

The team consists of Endocrinologist, Nephrologist, Kidney Surgeons and Pancreas Transplant Surgeons.

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